ABSTRACT
The incidence and mortality of AIDS have been decreasing after the adoption of combined antiretroviral therapy strategy in the world,then AIDS has become a manageable chronic infectious disease.But HIV/AIDS continues to be a major global public health problem since it is restricted by a variety of factors.The major reason for the persistence of HIV/AIDS is the inability of existing treatments to clear or eradicate the multiple HIV reservoirs that exist in the human body.To suppress the virus replication and rebound,HIV/AIDS patients must take life-long antiviral medications.A few years ago,the clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9)system has been developed as a simple,fast and easy to operate gene-editing technique.Several studies in HIV infected cells and/or in animal models have shown that the system has the potential to eliminate or disrupt HIV-integrated genome or HIV-infected cells from multiple HIV reservoirs,which may result in the complete cure of HIV/AIDS.This paper analyzes the results of CRISPR/CAS9 in the elimination of latent HIV,and discusses the possible problems and trends.
ABSTRACT
By the end of 2015,all over the world there were around 17 million HIV/AIDS cases received antiretroviral therapy,the HIV-1 morbidity and mortality decreased rapidly.With antiretroviral treatment to all HIV infected persons,HIV resistance mutation is also a threat to the long-term treatment and also,had a negative impact on the important public health strategy of the global elimination in 2030.This review attempts to proceed from different economic and geographical environment,describing genetic barrier of commonly used antiretroviral drugs,the degree of their cross-reactions,and the epidemiology and management of drug-resistant mutations from the individual and group levels.The paper also summarizes the prevalent modes of transmitted drug resistance (TDR) and acquired drug resistance (ADR) in both high-income and low-and middle-income countries (LMICs),and analyze the two kind problems of public health significance to HIV resistant mutations,i.e.pretreatment resistance (PDR) and preexposure prophylaxis (PREP).In addition,in view of effectivel HIV cases of treatment and management in different countries,this paper also analyzes the genotypic resistance testing and treatment practices related to AIDS prevention and control.The content has a certain reference function to our country.
ABSTRACT
<p><b>BACKGROUND</b>One of the major characteristics of the human immunodeficiency virus type 1 (HIV-1) is its unusually high degree of genetic variability, which involves in genetic diagnosis, subtyping, vaccine design, and epidemiology. HIV-1 CRF01_AE is a main prevalent HIV-1 recombinant strain in China. In this study, three full-length CRF01_AE genomes from Fujian Province, China were cloned, sequenced, and analyzed; and the further genetic diversity defining and epidemiologic analysis were carried out.</p><p><b>METHODS</b>Proviral DNA was extracted from non-cultured peripheral blood mononuclear cells, the near full-length HIV-1 genome was amplified and the PCR products were cloned into pCR-XL-TOPO vector and sequenced. 5'-long terminal repeat (LTR) and 3'-LTRs were amplified by additional independent PCR and cloned into pMD18T vector. Gene-based phylogenic tree was constructed and genetic distances were calculated by MEGA 3.1. Simplot was used for Bootscan analysis.</p><p><b>RESULTS</b>The phylogeny and genetic distance analysis of the three near full-length sequences confirmed that these three samples clustered with CRF01_AE isolates, more close to Thailand CRF01_AE strain CM240, and were distantly related to African CRF01_AE strain 90CF402. Analysis of their genomic organization revealed the presence of nine potential open reading frames. There were no major deletions, rearrangements, or insertions in the three sequences, but an in-frame stop codon was found in tat gene of Fj051. LTRs of the three sequences contained a few nucleotides mutation. We did not find new mosaic recombinant in the three sequences. The V3 motif was GPGQ in all the three sequences, and there were only few amino acids differences in all three V3 loop sequences.</p><p><b>CONCLUSION</b>This report reveals the background of the three full-length CRF01_AE genomes, the most dominantly circulating HIV-1 strain in Fujian Province, China. The work is essential for the design and development of an effective AIDS vaccine for the region.</p>